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Gabapentin (sold under the brand name Neurontin, among others) is a medication which is used to treat partial seizures, neuropathic pain, hot flashes, and restless legs syndrome.
Common side effects of gabapentin include sleepiness and dizziness.
Gabapentin was first approved for use in 1993;
Contents
1 Medical uses
1.1 Seizures
1.2 Neuropathic pain
1.3 Migraine
1.4 Anxiety disorders
1.5 Other uses
2 Side effects
2.1 Suicide
2.2 Cancer
2.3 Abuse and addiction
2.4 Withdrawal syndrome
3 Overdose
4 Pharmacology
4.1 Pharmacodynamics
4.2 Pharmacokinetics
4.2.1 Absorption
4.2.2 Distribution
4.2.3 Metabolism
4.2.4 Elimination
5 Chemistry
5.1 Synthesis
6 History
7 Society and culture
7.1 Sales
7.2 FDA approval
7.3 Off-label promotion
7.3.1 Franklin v. Pfizer case
7.4 Brand names
7.5 Related drugs
7.6 Recreational use
8 Veterinary use
9 References
10 External links
Medical uses
Gabapentin is used primarily to treat seizures and neuropathic pain.
Seizures
Gabapentin is approved for treatment of focal seizures
Neuropathic pain
A 2018 review found that gabapentin was of no benefit in sciatica nor low back pain.
A 2010 European Federation of Neurological Societies task force clinical guideline recommended gabapentin as a first-line treatment for diabetic neuropathy, postherpetic neuralgia, or central pain. It found good evidence that a combination of gabapentin and morphine or oxycodone or nortriptyline worked better than either drug alone; the combination of gabapentin and venlafaxine may be better than gabapentin alone.
A 2017 Cochrane review found evidence of moderate quality showing a reduction in pain by 50% in about 15% of people with postherpetic neuralgia and diabetic neuropathy.
A 2010 review found that it may be helpful in neuropathic pain due to cancer.
A 2009 review found gabapentin may reduce opioid use following surgery, but does not help with post-surgery chronic pain.
It appears to be as effective as pregabalin for neuropathic pain and costs less.
Migraine
The American Headache Society (AHS) and American Academy of Neurology (AAN) guidelines classify gabapentin as a drug with “insufficient data to support or refute use for migraine prophylaxis.”
Anxiety disorders
Gabapentin has been used off-label for the treatment of anxiety disorders. However, there is dispute over whether evidence is sufficient to support it being routinely prescribed for this purpose.
Other uses
Gabapentin may be useful in the treatment of comorbid anxiety in bipolar patients (however, not the manic or depressive episodes themselves).
Gabapentin is not effective alone as a mood-stabilizing treatment for bipolar disorder.
Side effects
The most common side effects of gabapentin include dizziness, fatigue, drowsiness, ataxia, peripheral edema (swelling of extremities), nystagmus, and tremor.
Suicide
In 2009 the U.S. Food and Drug Administration (FDA) issued a warning of an increased risk of suicidal thoughts and behaviors in patients taking some anticonvulsant drugs, including gabapentin,
Cancer
An increase in formation of adenocarcinomas was observed in rats during preclinical trials; however, the clinical significance of these results remains undetermined. Gabapentin is also known to induce pancreatic acinar cell carcinomas in rats through an unknown mechanism, perhaps by stimulation of DNA synthesis; these tumors did not affect the lifespan of the rats and did not metastasize.
Abuse and addiction
Surveys suggest that approximately 1.1 percent of the general population and 22 percent of those attending addiction facilities have a history of abuse of gabapentin.
Withdrawal syndrome
See also: Pregabalin § Withdrawal symptoms
Tolerance and withdrawal symptoms are a common occurrence in prescribed therapeutic users as well as non-medical recreational users. Withdrawal symptoms typically emerge within 12 hours to 7 days after stopping gabapentin.
Overdose
Through excessive ingestion, accidental or otherwise, persons may experience overdose symptoms including drowsiness, sedation, blurred vision, slurred speech, somnolence and possibly death, if a very high amount was taken, particularly if combined with alcohol. For overdose considerations, serum gabapentin concentrations may be measured for confirmation.
Pharmacology
Pharmacodynamics
Gabapentin is a gabapentinoid, or a ligand of the auxiliary α 2 δ subunit site of certain voltage-dependent calcium channels (VDCCs), and thereby acts as an inhibitor of α 2 δ subunit-containing VDCCs.
In one study, the affinity (K i ) value of gabapentin for the α 2 δ subunit expressed in rat brain was found to be about 50 nM.
Pharmacokinetics
Absorption
Gabapentin is absorbed from the intestines by an active transport process mediated via the large neutral amino acid transporter 1 (LAT1, SLC7A5), a transporter for amino acids such as L -leucine and L -phenylalanine.
The oral bioavailability of gabapentin is approximately 80% at 100 mg administered three times daily once every 8 hours, but decreases to 60% at 300 mg, 47% at 400 mg, 34% at 800 mg, 33% at 1,200 mg, and 27% at 1,600 mg, all with the same dosing schedule.
Gabapentin at a low dose of 100 mg has a T max (time to peak levels ) of approximately 1.7 hours, while the T max increases to 3 to 4 hours at higher doses.
Distribution
Gabapentin crosses the blood–brain barrier and enters the central nervous system.
Metabolism
Gabapentin undergoes little or no metabolism.
Elimination
Gabapentin is eliminated renally in the urine.
Chemistry
Chemical structures of GABA, gabapentin, and two other gabapentinoids, pregabalin and phenibut.
Gabapentin was designed by researchers at Parke-Davis to be an analogue of the neurotransmitter GABA that could more easily cross the blood–brain barrier.
Synthesis
A chemical synthesis of gabapentin has been described.
History
Gabapentin was developed at Parke-Davis and was first described in 1975.
Society and culture
Sales
Gabapentin is best known under the brand name Neurontin manufactured by Pfizer subsidiary Parke-Davis. A Pfizer subsidiary named Greenstone markets generic gabapentin.
In December 2004 the FDA granted final approval to a generic equivalent to Neurontin made by the Israeli firm Teva.
Neurontin began as one of Pfizer’s best selling drugs; however, Pfizer was criticized and under litigation for its marketing of the drug. Pfizer faced allegations that Parke-Davis marketed the drug for at least a dozen off-label uses that the FDA had not approved.
FDA approval
Gabapentin was originally approved by the U.S. Food and Drug Administration (FDA) in December 1993, for use as an adjuvant (effective when added to other antiseizure drugs) medication to control partial seizures in adults; that indication was extended to children in 2000.
Off-label promotion
Although some small, non-controlled studies in the 1990s—mostly sponsored by gabapentin’s manufacturer—suggested that treatment for bipolar disorder with gabapentin may be promising, Subsequent to the corporate acquisition of the original patent holder, the pharmaceutical company Pfizer admitted that there had been violations of FDA guidelines regarding the promotion of unproven off-label uses for gabapentin in the Franklin v. Pfizer case.
Reuters reported on 25 March 2010, that “Pfizer Inc violated federal racketeering law by improperly promoting the epilepsy drug Neurontin… Under federal RICO law the penalty is automatically tripled, so the finding will cost Pfizer $141 million.”
Bloomberg News reported “during the trial, Pfizer argued that Kaiser doctors continued to prescribe the drug even after the health insurer sued Pfizer in 2005. The insurer’s website also still lists Neurontin as a drug for neuropathic pain, Pfizer lawyers said in closing argument.”
The Wall Street Journal noted that Pfizer spokesman Christopher Loder said, “We are disappointed with the verdict and will pursue post-trial motions and an appeal.”
Franklin v. Pfizer case
Main article: Franklin v. Parke-Davis
According to the San Francisco Chronicle, off-label prescriptions accounted for roughly 90 percent of Neurontin sales.
While off-label prescriptions are common for a number of drugs, marketing of off-label uses of a drug is not. In 2004, Warner-Lambert (which subsequently was acquired by Pfizer) agreed to plead guilty for activities of its Parke-Davis subsidiary, and to pay $430 million in fines to settle civil and criminal charges regarding the marketing of Neurontin for off-label purposes. The 2004 settlement was one of the largest in U.S. history, and the first off-label promotion case brought successfully under the False Claims Act.
Brand names
Gabapentin was originally marketed under the brand name Neurontin. Since it became generic, it has been marketed worldwide using over 300 different brand names.
A capsule of gabapentin.
Related drugs
Parke-Davis developed a drug called pregabalin as a successor to gabapentin.
A prodrug form ( gabapentin enacarbil )
Recreational use
Also known on the streets as “Johnnies” or “Gabbies”,
Veterinary use
In cats, gabapentin can be used as an analgesic in multi-modal pain management.
Gabapentin is also used for some animal treatments, but some formulations (especially liquid forms) meant for human use contain the sweetener xylitol, which is toxic to dogs.

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